Functional capacity, physical activity, and arterial stiffness in patients with systemic sclerosis.

OBJECTIVES: Systemic sclerosis (SSc) is a complex immune-mediated connective tissue disease, involving skin manifestations, vascular features, and organ-based complications that may affect functional capacity and physical activity. Functional capacity and physical activity are associated with arterial stiffness; however, this relationship has not been evaluated in patients with SSc. Therefore, the objective of this study was to investigate the association of functional capacity and physical activity with arterial stiffness in patients with SSc. METHODS: Sixty-five patients with SSc were enrolled in this cross-sectional study. Arterial stiffness was evaluated with carotid-femoral pulse wave velocity (cf-PWV). Functional capacity and physical activity were assessed with a six-min walk test (6MWT) and International Physical Activity Questionnaire-Short Form (IPAQ-SF), respectively. RESULTS: All participants were women, and the mean age was 54.91 ± 11.18 years. 6MWT distance and IPAQ-SF were inversely associated with cf-PWV in crude analysis (p < 0.05). The relationship between 6MWT distance and cf-PWV was maintained in the fully adjusted model (ß = - 0.007, 95% CI, - 0.013 to 0.000). Similarly, the association between IPAQ-SF and cf-PWV remained significant in the fully adjusted model (ß = - 0.001, 95% CI, - 0.002 to - 0.001). CONCLUSION: The present study indicates that functional capacity and self-reported physical activity are independently associated with arterial stiffness in patients with SSc. Exercise interventions targeted to increase functional capacity and physical activity may help to regulate arterial stiffness in patients with SSc. Key Points • Arterial stiffness is an independent predictor of cardiovascular risk. • SSc patients exhibit decreased exercise capacity and functional capacity. • The association of functional capacity and physical activity with arterial stiffness in patients with SSc is unknown. • Functional capacity and self-reported physical activity are independently associated with arterial stiffness in patients with SSc.

Determinants of Six-Minute Walk Test Performance in Women with Systemic Sclerosis.

OBJECTIVES: The aim of this study was to investigate the determinants of six-minute walk test (6MWT) distance in women with systemic sclerosis. METHODS: In this cross-sectional study, 36 women with systemic sclerosis were assessed using the Medsger Systemic Sclerosis Severity Scale (MSS), modified Rodnan Skin Score (mRSS), Health Assessment Questionnaire (HAQ), University of California Scleroderma Clinical Study Consortium Gastrointestinal Tract Scale, quadriceps strength measurement, Milliken Activities of Daily Living Scale (MAS), and International Physical Activity Questionnaire. The 6MWT was performed to assess the participants' functional capacity and examine factors affecting functional capacity. RESULTS: 6MWT distance was moderately associated with disease severity, with 14 participants walking less than 80% of the predicted distance. 6MWT distance was also significantly correlated with spirometry values and MSS, mRSS, HAQ, and MAS scores (p<0.05). In linear regression analysis, MSS and MAS scores were identified as independent predictors of 6MWD and accounted for 42.5% of variance (R2 = 0.425). CONCLUSION: Disease severity and activities of daily living are independently associated with functional capacity in women with scleroderma, with MSS and MAS scores accounting for 42.5% of variance in 6MWT distance in the linear regression model.

Extended autoantibody panel in Turkish patients with early-stage systemic sclerosis: Coexpressions and their influences on clinical phenotypes.

BACKGROUND/AIM: To investigate the frequency and clinical relevance of an extended autoantibody profile in patients with systemic sclerosis (SSc). MATERIALS AND METHODS: In this cross-sectional study, serum from 100 consecutive patients was subjected to indirect immunofluorescence (IIF) (HEp-20-10/primate liver mosaic) and Systemic Sclerosis Profile by EUROIMMUN to evaluate anti-nuclear antibodies (ANA) and autoantibodies against 13 different autoantibodies in patients with SSc less than 3 years. RESULTS: Ninety-three of 100 patients were positive for ANA by IIF. Fifty-three patients showed single positivity, 26 anti-topoisomerase antibodies (anti-Scl70 ab), 16 anticentromere antibodies (ACAs), six anti-RNA polymerase III antibodies (anti-RNAPIII ab), one anti-Ku antibody, one anti-PM/Scl100 antibody, two anti-PM/Scl75 antibodies, one anti-Ro52 antibody, whereas 32 patients had multiple autoantibody positivities. Among classic SSc-specific autoantibodies, anti-Scl70 and anti-RNAPIII abs showed the highest cooccurrence (n = 4). One patient was simultaneously positive for anti-RNAPIII ab and ACA, and one was positive for ACA and anti-Scl70 ab. The clinical features were not statistically different between single and multiple autoantibody-positivity for classic SSc-specific autoantibodies (ACA, anti-Scl70 ab, and anti-RNAPIII ab), except for digital ulcer in the multiantibody positive ACA group (p = .019). CONCLUSION: Based on our results, coexpression of autoantibodies is not uncommon in SSc patients. Although autoantibodies specific to SSc in early disease show generally known clinical features, it remains to be investigated how the coexpression of autoantibodies will affect clinical presentation.

Treatment of systemic sclerosis-associated digital ulcers: recommendations of the Turkish Society for Rheumatology.

OBJECTIVES: Digital ulcers (DUs) are associated with a significant burden in systemic sclerosis (SSc) by leading to severe pain, physical disability, and reduced quality of life. This effort aimed to develop recommendations of the Turkish Society for Rheumatology (TRD) on the management of DUs associated with SSc. METHODS: In the first meeting held in December 2020 with the participation of a task force consisting of 23 rheumatologists the scope of the recommendations and research questions were determined. A systematic literature review was conducted by 5 fellows and results were presented to the task force during the second meeting. The Oxford system was used to determine the level of evidence. The preliminary recommendations were discussed, modified, and voted by the task force and then by members of TRD via e-mail invitation allowing personalised access to a web-based questionnaire [SurveyMonkey®]. RESULTS: A total of 23 recommendations under 7 main headings were formulated covering non-pharmacological measures for the prevention of DUs and pharmacological treatments including vasodilators, anti-aggregants, antibiotics, wound care, pain control, and interventions including sympathectomy, botulinum toxin, and surgery. Risk factors, poor prognostic factors, prevention of DU and adverse effects of medical treatments were reported as 4 overarching principles. CONCLUSIONS: These evidence-based recommendations for the management of SSc-associated DUs were developed to provide a useful guide to all physicians who are involved in the care of patients with SSc, as well as to point out unmet needs in this field.

Vitamin D attenuates elevated oxidative DNA damage in scleroderma patients with organ involvement: A prospective study.

Scleroderma is a rare autoimmune disease characterized by progressive fibrosis of the skin and internal organs. Oxidative damage to macromolecules has been reported to occur in scleroderma. Among the macromolecular damages, oxidative DNA damage is a sensitive and cumulative marker of oxidative stress and is of particular interest because of its cytotoxic and mutagenic effects. Vitamin D supplementation is an important part of treatment, as vitamin D deficiency is a common problem in scleroderma. Furthermore, the antioxidant role of vitamin D has been demonstrated in recent studies. In light of this information, the present study aimed to comprehensively investigate oxidative DNA damage in scleroderma at baseline and to evaluate the contribution of vitamin D supplementation to the attenuation of DNA damage in a prospectively designed study. In accordance with these objectives, oxidative DNA damage in scleroderma was evaluated by measurement of stable damage products (8-oxo-dG, S-cdA, and R-cdA) in urine by liquid chromatography-tandem mass spectrometry (LC-MS/MS); serum vitamin D levels were determined by high-resolution mass spectrometry (HR-MS); VDR gene expression and four polymorphisms in the VDR gene (rs2228570, rs1544410, rs7975232, and rs731236) were analyzed by RT-PCR and compared with healthy subjects. In the prospective part, the DNA damage and the VDR expression of the patients who received vitamin D were re-evaluated after the replacement. As a result of this study, we demonstrated that all DNA damage products were increased in scleroderma patients compared to healthy controls, whereas vitamin D levels and VDR expression were significantly lower (p < 0.05). After supplementation, statistical significance (p < 0.05) was reached for the decrease in 8-oxo-dG and the increase in VDR expression. Attenuated 8-oxo-dG after replacement in patients with lung, joint, and gastrointestinal system involvement demonstrated the efficacy of vitamin D in scleroderma patients with organ involvement. To the best of our knowledge, this is the first study to examine oxidative DNA damage in scleroderma comprehensively and to evaluate the effects of vitamin D on DNA damage using a prospective design.

Evaluation of middle ear and hearing status of ankylosing spondylitis patients with wideband tympanometry and pure tone audiometry tests.

OBJECTIVES: The aim of this study was to evaluate the middle and inner ear function and hearing status of Ankylosing spondylitis (AS) patients. METHODS: One hundred twenty-four ears of 62 patients with AS and 90 ears (control group) of 45 healthy subjects were included in the study. The hearing levels of the participants were assessed with pure tone and high-frequency audiometry at the octave frequency between 250 and 16,000 Hz. The absorbance rates and resonance frequencies of middle ear were measured with the wideband tympanometry (WBT) test. AS group was divided into subgroups based on the disease activity, duration of follow-up, medications used for AS, and the subgroups were compared according to hearing status and absorbance and resonance frequencies of middle ears. RESULTS: A statistically significant difference was found between the AS and control groups in terms of air and bone conduction thresholds at frequencies of 250, 500, 1000, 2000, and 4000 Hz and the mean PTA1, PTA2, and PTA3 values (p < 0.05). In contrast, no statistically significant difference was observed between two groups in terms of high-frequency thresholds (8000-16,000 Hz). Although the middle ear resonance frequency obtained from the WBT test was higher in the AS group compared to the control group, no significant difference was observed (p > 0.05). The severity of disease adversely affected the hearing threshold at 250, and 500 Hz for air conduction, at 500 Hz for bone conduction threshold, and at PTA1 (p < 0.05). The duration and severity of disease did not affect absorbance values of WBT (p > 0.05). CONCLUSION: To our knowledge, this is the first study to demonstrate the effects of AS patients on the middle ear function with WBT and to report middle ear absorbance values and resonance frequency changes in AS patients. The higher resonance frequency values found by WBT in AS patients may be due to the stiffness that develops as a result of middle ear involvement. According to pure tone and high-frequency audiometry findings, it has been seen that AS leads to SNHL especially at low frequencies.

Comparison of physiological responses after incremental shuttle walking test and 6-minute walk test in patients with systemic sclerosis.

BACKGROUND: The 6­minute walk test (6MWT) is a commonly used to evaluate exercise capacity in patients with systemic sclerosis (SSc), but there was no study using the incremental shuttle walking test (ISWT) for assessing exercise capacity and comparing the patient's cardiorespiratory responses to these tests. The aim was to investigate the usability and determinants of the ISWT in patients with SSc and compare the physiological responses after the ISWT and 6MWT. METHODS: A total of thirty four female patients with SSc were included. Dyspnea during daily activities and knee extensor muscle strength was assessed, skin fibrosis and disease severity were recorded, and 6MWT and ISWT were carried out for the exercise capacity measurement. Pulmonary function test results were recorded from the individuals' medical records for SSc with interstitial lung disease (SSc-ILD) patients. RESULTS: The ISWT distance was significantly correlated with the 6MWT distance (p < 0.001). The 6MWT was correlated with age, modified Rodnan skin score, Medsger severity score, modified British Medical Research Council Questionnaire (mMRC) score, and knee extensor muscle strength (p < 0.05). The 6MWT was correlated with the forced expiratory volume in the first second (FEV1) (lt) and forced vital capacity (FVC) (lt) in patients with SSc-ILD (p < 0.05). The ISWT distance was correlated with age, modified Rodnan skin score, mMRC score, and knee extensor muscle strength (p < 0.05). Age, mMRC, and knee extensor muscle strength explained 33.8% of the variance in 6MWT distance, while age, mMRC, and knee extensor muscle strength explained 51.7% of the variance in the ISWT distance. CONCLUSION: Because of the higher cardiopulmonary responses, and having a more standardized procedure, the ISWT may be preferable for investigating symptom-limited exercise capacity in patients with SSc. Age, dyspnea, and knee extensor muscle strength were the determinants of exercise capacity in patients with SSc.

Postural balance and fall risk in patients with systemic sclerosis: A cross-sectional study.

OBJECTIVES: This study aims to assess postural balance, fall risk, and the relationship of these parameters with disease-related factors in patients with systemic sclerosis (SSc). PATIENTS AND METHODS: Thirty patients with SSc (6 males, 24 females; mean age 51.1±10.6 years; range 35 to 65) and 30 healthy subjects (6 males, 24 females, mean age 52.4±8.7 years; range 35 to 65) matched for age, sex and body mass index were included in this cross-sectional study conducted between September 2018 and November 2019. Postural balance was measured with Biodex Balance SystemTM (Biodex-BS), Berg Balance Scale (BBS), and Timed Up and Go (TUG) test. Individuals' history of falls in the past year, functional capacity, lower limb muscles strength, pulmonary function, respiratory muscle strength, diffusion capacity, and dyspnea severity were evaluated. RESULTS: The SSc group had postural balance impairment and a higher fall frequency than the control group. The SSc group had significantly higher sway index on postural stability (0.6±0.5), lower directional control score (42.1±8.0), and longer test duration (51.8±11.8) on limit of stability of Biodex-BS, lower BBS score (51.5±4.9), and longer test duration on TUG test (8.3±2.7) than control group (all p<0.05). Also, SSc group exhibited significantly lower functional capacity, limb muscles strength, pulmonary function, respiratory muscles strength, diffusion capacity, and higher dyspnea severity than control group (all p<0.05). The postural balance and fall frequency of SSc patients were significantly associated with functional capacity, lower limb muscles strength, pulmonary function, respiratory muscle strength, diffusion capacity, and dyspnea severity. CONCLUSION: Our results suggest that postural balance impairment and fall risk should be assessed as they appear to be important problems in patients with SSc. Furthermore, assessment of functional capacity, lower limb muscles strength, and lung involvement may highlight those with postural balance impairment and higher fall risk.

Association between core stability and physical function, functional performance in patients with systemic sclerosis.

OBJECTIVE: To investigate the association of core stability with physical function and functional performance in patients with systemic sclerosis (SSc). METHODS: Forty patients who met the American College of Rheumatology / European League Against Rheumatism 2013 classification criteria for SSc were included in the cross-sectional study. For evaluation of core stability, trunk muscle endurance and trunk muscle strength were assessed. Trunk extensor and trunk flexor endurance tests were used for assessment of trunk muscle endurance. Trunk muscle strength was measured with a hand-held dynamometer and modified sit-up test. To measure physical function the Health Assessment Questionnaire Disability Index (HAQ-DI) and to measure functional performance 6-minute walking test (6MWT) and sit-to-stand test (STS) were used. RESULTS: Patients with SSc had lower mean trunk extensor and flexor endurance test times (49.87 ± 30.81 and 32.17 ± 15.42 seconds, respectively), modified sit-up test repetition (17.42 ± 7.81) and trunk extensor and flexor muscle strength (7.48 ± 2.29 kg and 6.20 ± 1.68 kg, respectively) when compared to the reference values in healthy individuals. All measurements were used to evaluate core stability associated with HAQ-DI score, 6DMWT walking distance and STS test duration (all P < .05). CONCLUSION: Patients with SSc have markedly reduced core stability and this negatively affects the physical function and functional performance. Therefore, this study highlights the importance of trunk muscle in patients with SSc. We suggest that not only upper-lower extremity muscles, but also trunk muscle strength and endurance should be measured and core stability exercises can be added to the training programs to maintain and/or improve physical functions and functional performance in SSc patients.

Fatigue and its relationship with disease-related factors in patients with systemic sclerosis: A cross-sectional study

Background/aim: Fatigue is very common symptom in patients with systemic sclerosis (SSc) and adversely affects health-related quality of life and the ability to perform daily living activities. This study aimed to determine the severity of fatigue, and its related factors, in patients with SSc. Materials and methods: A total of 35 patients with SSc (6 males and 29 females, mean age of 50.71 ± 10.09 years) and 35 healthy control subjects (8 males and 27 females, mean age of 54.14 ± 9.51 years) were included in this study. The Fatigue Impact Scale for fatigue, Modified Medical Research Council Scale for dyspnea severity, 6-Minute Walking Test for functional capacity, Health Assessment Questionnaire Disability Index, Scleroderma Health Assessment Questionnaire and Short Form-36 Quality of Life Questionnaire for health-related quality of life were used in the evaluation of the subjects. Furthermore, pulmonary functions, diffusion capacity, and respiratory and peripheral muscle strength were evaluated. Results: Of the SSc patients, 80% experienced fatigue and presented with higher total and cognitive, physical, and psychosocial subscale fatigue scores than the healthy control subjects (P < 0.05). Moreover, the SSc patients exhibited significantly increased dyspnea severity, impaired pulmonary function-diffusion capacity, decreased respiratory-peripheral muscle strength, reduced functional capacity, and worsened health-related quality of life when compared to the control group (P < 0.05). Fatigue in the SSc group was significantly associated with age, dyspnea severity, diffusion capacity, respiratory and peripheral muscle strength, functional capacity, and health- related quality of life (P < 0.05). Conclusions: Along with the decrease in diffusion capacity, increase dyspnea, a decrease in both peripheral and respiratory muscle strength, and worsening functional capacity may have an effect on increased fatigue in SSc patients. Increased fatigue can also affect the life quality and daily life activities of a patient. Therefore, multidisciplinary approaches are recommended to evaluate and improve these parameters in the treatment of fatigue from the early period in SSc patients.

Minor salivary gland evaluation: Sjögren's syndrome.

BACKGROUND/AIM:  We aimed to analyze the value of 3 serial sections, spaced 200 µm apart, for quantification of lymphocyte and plasma cell foci in minor salivary gland biopsy (MSGB). MATERIALS AND METHODS:  Labial MSGBs from 69 patients with Sjögren's syndrome (SS) and scleroderma were used for this study. Each sample was prepared as 3 serial sections spaced 200 µm apart. Lymphocytic and plasma cell focus score (LFS, PFS) were determined for each section, and the diagnostic results were compared to those obtained from a single section. RESULTS: For 22 of the 69 patients, all 3 sections were scored at <1 and interpreted as inconclusive for the presence of SS. For 20 cases, all 3 sections were scored at ≥1 and interpreted as diagnostic for SS. In the remaining 27 cases, the score was found to vary between sections. Plasma cell foci were observed in 11 cases, with 5 cases exhibiting a PFS of ≥1. Of those 5 cases, 4 also had a LFS of ≥1. CONCLUSION:  Assessment of 3 serial sections in MSGB has the potential to improve accuracy of SS diagnosis by detecting specific features that may not have been detected in a single section. We concluded that data about the PFS require further evaluation.